Cross‐Linking of Hydroxypropylcellulose With Flaxseed Rhamnogalacturonans Using Citric Acid Produces a Hemocompatible Biocomposite for <scp>pH</scp>‐Responsive Rifaximin Delivery

ABSTRACT Herein, we reported the esterification of flaxseed hydrogel (FSH) with hydroxypropyl cellulose (HPC) using citric acid (CA) as a cross‐linker. The stimuli (biomimetic) responsiveness to pH, temperature, saline, and solvents of the novel composite hydrogel, that is, CA crosslinked FSH and HPC (FSH‐CA‐HPC), was evaluated. Fourier transform infrared (FTIR) spectroscopic analysis witness the formation of FSH‐CA‐HPC. Scanning electron microscopic analysis indicated the porous nature of FSH‐CA‐HPC. At pH 6.8 and 7.4, and in deionized water (DW), FSH‐CA‐HPC exhibited significant swelling with a swelling order of DW &gt; pH 7.4 &gt; pH 6.8; however, at pH 1.2, negligible swelling of FSH‐CA‐HPC was noted. The FSH‐CA‐HPC also exhibited swelling/deswelling behavior when transferred from DW to ethanol, DW to normal saline (0.9% NaCl), and pH 7.4 (slightly basic) to pH 1.2 (acidic), respectively. The sustained release potential of FSH‐CA‐HPC was investigated after preparing tablets of rifaximin (RF) with FSH‐CA‐HPC. The FSH‐CA‐HPC‐based tablets sustained the release of RF for 8 h. The RF release followed first‐order kinetics and non‐Fickian diffusion. FSH‐CA‐HPC also showed nonthrombogenic and nonhemolytic behavior. Concluding, FSH‐CA‐HPC appeared as a smart and pH‐sensitive material for the targeted/sustained release of drugs, especially in the intestine.